# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9691 | 0 | 0.9996 | Defining pathogenic bacterial species in the genomic era. Actual definitions of bacterial species are limited due to the current criteria of definition and the use of restrictive genetic tools. The 16S ribosomal RNA sequence, for example, has been widely used as a marker for phylogenetic analyses; however, its use often leads to misleading species definitions. According to the first genetic studies, removing a certain number of genes from pathogenic bacteria removes their capacity to infect hosts. However, more recent studies have demonstrated that the specialization of bacteria in eukaryotic cells is associated with massive gene loss, especially for allopatric endosymbionts that have been isolated for a long time in an intracellular niche. Indeed, sympatric free-living bacteria often have bigger genomes and exhibit greater resistance and plasticity and constitute species complexes rather than true species. Specialists, such as pathogenic bacteria, escape these bacterial complexes and colonize a niche, thereby gaining a species name. Their specialization allows them to become allopatric, and their gene losses eventually favor reductive genome evolution. A pathogenic species is characterized by a gene repertoire that is defined not only by genes that are present but also by those that are lacking. It is likely that current bacterial pathogens will disappear soon and be replaced by new ones that will emerge from bacterial complexes that are already in contact with humans. | 2010 | 21687765 |
| 9477 | 1 | 0.9996 | The microbiome-shaping roles of bacteriocins. The microbiomes on human body surfaces affect health in multiple ways. They include not only commensal or mutualistic bacteria but also potentially pathogenic bacteria, which can enter sterile tissues to cause invasive infection. Many commensal bacteria produce small antibacterial molecules termed bacteriocins that have the capacity to eliminate specific colonizing pathogens; as such, bacteriocins have attracted increased attention as potential microbiome-editing tools. Metagenome-based and activity-based screening approaches have strongly expanded our knowledge of the abundance and diversity of bacteriocin biosynthetic gene clusters and the properties of a continuously growing list of bacteriocin classes. The dynamic acquisition, diversification or loss of bacteriocin genes can shape the fitness of a bacterial strain that is in competition with bacteriocin-susceptible bacteria. However, a bacteriocin can only provide a competitive advantage if its fitness benefit exceeds the metabolic cost of production, if it spares crucial mutualistic partner strains and if major competitors cannot develop resistance. In contrast to most currently available antibiotics, many bacteriocins have only narrow activity ranges and could be attractive agents for precision therapy and prevention of infections. A common scientific strategy involving multiple disciplines is needed to uncover the immense potential of microbiome-shaping bacteriocins. | 2021 | 34075213 |
| 9490 | 2 | 0.9996 | The superbugs: evolution, dissemination and fitness. Since the introduction of antibiotics, bacteria have not only evolved elegant resistance mechanisms to thwart their effect, but have also evolved ways in which to disseminate themselves or their resistance genes to other susceptible bacteria. During the past few years, research has revealed not only how such resistance mechanisms have been able to evolve and to rapidly disseminate, but also how bacteria have, in some cases, been able to adapt to this new burden of resistance with little or no cost to their fitness. Such adaptations make the control of these superbugs all the more difficult. | 1998 | 10066531 |
| 9688 | 3 | 0.9995 | Indirect Selection against Antibiotic Resistance via Specialized Plasmid-Dependent Bacteriophages. Antibiotic resistance genes of important Gram-negative bacterial pathogens are residing in mobile genetic elements such as conjugative plasmids. These elements rapidly disperse between cells when antibiotics are present and hence our continuous use of antimicrobials selects for elements that often harbor multiple resistance genes. Plasmid-dependent (or male-specific or, in some cases, pilus-dependent) bacteriophages are bacterial viruses that infect specifically bacteria that carry certain plasmids. The introduction of these specialized phages into a plasmid-abundant bacterial community has many beneficial effects from an anthropocentric viewpoint: the majority of the plasmids are lost while the remaining plasmids acquire mutations that make them untransferable between pathogens. Recently, bacteriophage-based therapies have become a more acceptable choice to treat multi-resistant bacterial infections. Accordingly, there is a possibility to utilize these specialized phages, which are not dependent on any particular pathogenic species or strain but rather on the resistance-providing elements, in order to improve or enlengthen the lifespan of conventional antibiotic approaches. Here, we take a snapshot of the current knowledge of plasmid-dependent bacteriophages. | 2021 | 33572937 |
| 9581 | 4 | 0.9995 | Lateral gene transfer, bacterial genome evolution, and the Anthropocene. Lateral gene transfer (LGT) has significantly influenced bacterial evolution since the origins of life. It helped bacteria generate flexible, mosaic genomes and enables individual cells to rapidly acquire adaptive phenotypes. In turn, this allowed bacteria to mount strong defenses against human attempts to control their growth. The widespread dissemination of genes conferring resistance to antimicrobial agents has precipitated a crisis for modern medicine. Our actions can promote increased rates of LGT and also provide selective forces to fix such events in bacterial populations. For instance, the use of selective agents induces the bacterial SOS response, which stimulates LGT. We create hotspots for lateral transfer, such as wastewater systems, hospitals, and animal production facilities. Conduits of gene transfer between humans and animals ensure rapid dissemination of recent transfer events, as does modern transport and globalization. As resistance to antibacterial compounds becomes universal, there is likely to be increasing selection pressure for phenotypes with adverse consequences for human welfare, such as enhanced virulence, pathogenicity, and transmission. Improved understanding of the ecology of LGT could help us devise strategies to control this fundamental evolutionary process. | 2017 | 27706829 |
| 9489 | 5 | 0.9995 | The origins of antibiotic resistance. Antibiotics remain one of our most important pharmacological tools for the control of infectious disease. However, unlike most other drugs, the use of antibiotics selects for resistant organisms and erodes their clinical utility. Resistance can emerge within populations of bacteria by mutation and be retained by subsequent selection or by the acquisition of resistance elements laterally from other organisms. The source of these resistance genes is only now being understood. The evidence supports a large bacterial resistome-the collection of all resistance genes and their precursors in both pathogenic and nonpathogenic bacteria. These genes have arisen by various means including self-protection in the case of antibiotic producers, transport of small molecules for various reasons including nutrition and detoxification of noxious chemicals, and to accomplish other goals, such as metabolism, and demonstrate serendipitous selectivity for antibiotics. Regardless of their origins, resistance genes can rapidly move through bacterial populations and emerge in pathogenic bacteria. Understanding the processes that contribute to the evolution and selection of resistance is essential to mange current stocks of antibiotics and develop new ones. | 2012 | 23090593 |
| 9687 | 6 | 0.9995 | Spread of organisms with novel genotypes: thoughts from an ecological perspective. One category of objection to the release of organisms produced by genetic engineering is based on the fear that such organisms may persist in the environment and damage existing ecosystems. An assessment of environmental risk thus involves an ecological question analogous to the introduction of exotic species which has been known to produce serious ecological disruptions. An investigation of the literature on exotic introductions reveals, however, that foreign species do not invariably produce adverse changes. Ecologists believe that only a fraction of immigrating species actually produces ecological dislocation while the majority probably fail to penetrate existing biotic assemblages. Stressed or simplified environments are, however, more vulnerable to successful invasion. Unfortunately, because very little information has ever been collected to document the number or causes of failed introductions, it is impossible to quantify the probability that any introduced species will or will not cause serious disturbance purely on the basis of historical evidence. The development and spread of genotypes that confer resistance to chemical control agents in insects and microorganisms is also analogous to genetic engineering in that human activity contributes to the spread of new genotypes. In both groups of organisms, resistant genotypes can come to predominate in even geographically widespread populations with great rapidity. Resistance to pesticides in insects is usually found to be determined by single genes. In bacteria, antibiotic resistance genes are usually, if not always, associated with the extrachromosomal genetic elements known as plasmids. Bacteria seem to be able to transmit plasmid-borne genes between species and genera with facility. The ease with which new genes can be inserted into bacteria via plasmid vectors in recombinant technology is thus a two-edged sword. It may be very difficult to keep inserted genes isolated in single bacterial strains. The evaluation of the literature on which this report is based suggests that an ecological approach for risk assessment is appropriate. Microorganisms, for which genetic engineering is of most immediate importance, exhibit the same ecological properties as higher organisms. The proportion of an organism's genome which is novel has no direct correlation with the magnitude of impact such a change may have in economic, medical, or ecological terms. Meaningful probabilities for persistence of engineered organisms in the environment will have to be generated by experiment, probably with model microbial ecosystems. | 1983 | 6576449 |
| 9481 | 7 | 0.9995 | Genetic linkage and horizontal gene transfer, the roots of the antibiotic multi-resistance problem. Bacteria carrying resistance genes for many antibiotics are moving beyond the clinic into the community, infecting otherwise healthy people with untreatable and frequently fatal infections. This state of affairs makes it increasingly important that we understand the sources of this problem in terms of bacterial biology and ecology and also that we find some new targets for drugs that will help control this growing epidemic. This brief and eclectic review takes the perspective that we have too long thought about the problem in terms of treatment with or resistance to a single antibiotic at a time, assuming that dissemination of the resistance gene was affected by simple vertical inheritance. In reality antibiotic resistance genes are readily transferred horizontally, even to and from distantly related bacteria. The common agents of bacterial gene transfer are described and also one of the processes whereby nonantibiotic chemicals, specifically toxic metals, in the environment can select for and enrich bacteria with antibiotic multiresistance. Lastly, some speculation is offered on broadening our perspective on this problem to include drugs directed at compromising the ability of the mobile elements themselves to replicate, transfer, and recombine, that is, the three "infrastructure" processes central to the movement of genes among bacteria. | 2006 | 17127524 |
| 9586 | 8 | 0.9995 | Antibiotic resistance. Through billions of years of evolution, microbes have developed myriad defense mechanisms designed to ensure their survival. This protection is readily transferred to their fellow life forms via transposable elements. Despite very early warnings, humans have chosen to abuse the gift of antibiotics and have created a situation where all microorganisms are resistant to some antibiotics and some microorganisms are resistant to all antibiotics. When antibiotics are used, six events may occur with only one being beneficial: when the antibiotic aids the host defenses to gain control and eliminate the infection. Alternatively, the antibiotic may cause toxicity or allergy, initiate a superinfection with resistant bacteria, promote microbial chromosomal mutations to resistance, encourage resistance gene transfer to susceptible species, or promote the expression of dormant resistance genes. | 2003 | 14664456 |
| 8327 | 9 | 0.9995 | 'Big things in small packages: the genetics of filamentous phage and effects on fitness of their host'. This review synthesizes recent and past observations on filamentous phages and describes how these phages contribute to host phentoypes. For example, the CTXφ phage of Vibrio cholerae encodes the cholera toxin genes, responsible for causing the epidemic disease, cholera. The CTXφ phage can transduce non-toxigenic strains, converting them into toxigenic strains, contributing to the emergence of new pathogenic strains. Other effects of filamentous phage include horizontal gene transfer, biofilm development, motility, metal resistance and the formation of host morphotypic variants, important for the biofilm stress resistance. These phages infect a wide range of Gram-negative bacteria, including deep-sea, pressure-adapted bacteria. Many filamentous phages integrate into the host genome as prophage. In some cases, filamentous phages encode their own integrase genes to facilitate this process, while others rely on host-encoded genes. These differences are mediated by different sets of 'core' and 'accessory' genes, with the latter group accounting for some of the mechanisms that alter the host behaviours in unique ways. It is increasingly clear that despite their relatively small genomes, these phages exert signficant influence on their hosts and ultimately alter the fitness and other behaviours of their hosts. | 2015 | 25670735 |
| 9294 | 10 | 0.9995 | Plasmid persistence: costs, benefits, and the plasmid paradox. Plasmids are extrachromosomal DNA elements that can be found throughout bacteria, as well as in other domains of life. Nonetheless, the evolutionary processes underlying the persistence of plasmids are incompletely understood. Bacterial plasmids may encode genes for traits that are sometimes beneficial to their hosts, such as antimicrobial resistance, virulence, heavy metal tolerance, and the catabolism of unique nutrient sources. In the absence of selection for these traits, however, plasmids generally impose a fitness cost on their hosts. As such, plasmid persistence presents a conundrum: models predict that costly plasmids will be lost over time or that beneficial plasmid genes will be integrated into the host genome. However, laboratory and comparative studies have shown that plasmids can persist for long periods, even in the absence of positive selection. Several hypotheses have been proposed to explain plasmid persistence, including host-plasmid co-adaptation, plasmid hitchhiking, cross-ecotype transfer, and high plasmid transfer rates, but there is no clear evidence that any one model adequately resolves the plasmid paradox. | 2018 | 29562144 |
| 4256 | 11 | 0.9995 | Genetic competence and transformation in oral streptococci. The oral streptococci are normally non-pathogenic residents of the human microflora. There is substantial evidence that these bacteria can, however, act as "genetic reservoirs" and transfer genetic information to transient bacteria as they make their way through the mouth, the principal entry point for a wide variety of bacteria. Examples that are of particular concern include the transfer of antibiotic resistance from oral streptococci to Streptococcus pneumoniae. The mechanisms that are used by oral streptococci to exchange genetic information are not well-understood, although several species are known to enter a physiological state of genetic competence. This state permits them to become capable of natural genetic transformation, facilitating the acquisition of foreign DNA from the external environment. The oral streptococci share many similarities with two closely related Gram-positive bacteria, S. pneumoniae and Bacillus subtilis. In these bacteria, the mechanisms of quorum-sensing, the development of competence, and DNA uptake and integration are well-characterized. Using this knowledge and the data available in genome databases allowed us to identify putative genes involved in these processes in the oral organism Streptococcus mutans. Models of competence development and genetic transformation in the oral streptococci and strategies to confirm these models are discussed. Future studies of competence in oral biofilms, the natural environment of oral streptococci, will be discussed. | 2001 | 11497374 |
| 9474 | 12 | 0.9995 | Broadscale phage therapy is unlikely to select for widespread evolution of bacterial resistance to virus infection. Multi-drug resistant bacterial pathogens are alarmingly on the rise, signaling that the golden age of antibiotics may be over. Phage therapy is a classic approach that often employs strictly lytic bacteriophages (bacteria-specific viruses that kill cells) to combat infections. Recent success in using phages in patient treatment stimulates greater interest in phage therapy among Western physicians. But there is concern that widespread use of phage therapy would eventually lead to global spread of phage-resistant bacteria and widespread failure of the approach. Here, we argue that various mechanisms of horizontal genetic transfer (HGT) have largely contributed to broad acquisition of antibiotic resistance in bacterial populations and species, whereas similar evolution of broad resistance to therapeutic phages is unlikely. The tendency for phages to infect only particular bacterial genotypes limits their broad use in therapy, in turn reducing the likelihood that bacteria could acquire beneficial resistance genes from distant relatives via HGT. We additionally consider whether HGT of clustered regularly interspaced short palindromic repeats (CRISPR) immunity would thwart generalized use of phages in therapy, and argue that phage-specific CRISPR spacer regions from one taxon are unlikely to provide adaptive value if horizontally-transferred to other taxa. For these reasons, we conclude that broadscale phage therapy efforts are unlikely to produce widespread selection for evolution of bacterial resistance. | 2020 | 33365149 |
| 9482 | 13 | 0.9995 | Gene flow, mobile genetic elements and the recruitment of antibiotic resistance genes into Gram-negative pathogens. Antibiotics were one of the great discoveries of the 20th century. However, resistance appeared even in the earliest years of the antibiotic era. Antibiotic resistance continues to become worse, despite the ever-increasing resources devoted to combat the problem. One of the most important factors in the development of resistance to antibiotics is the remarkable ability of bacteria to share genetic resources via Lateral Gene Transfer (LGT). LGT occurs on a global scale, such that in theory, any gene in any organism anywhere in the microbial biosphere might be mobilized and spread. With sufficiently strong selection, any gene may spread to a point where it establishes a global presence. From an antibiotic resistance perspective, this means that a resistance phenotype can appear in a diverse range of infections around the globe nearly simultaneously. We discuss the forces and agents that make this LGT possible and argue that the problem of resistance can ultimately only be managed by understanding the problem from a broad ecological and evolutionary perspective. We also argue that human activities are exacerbating the problem by increasing the tempo of LGT and bacterial evolution for many traits that are important to humans. | 2011 | 21517914 |
| 9237 | 14 | 0.9995 | The gossip paradox: Why do bacteria share genes? Bacteria, in contrast to eukaryotic cells, contain two types of genes: chromosomal genes that are fixed to the cell, and plasmids, smaller loops of DNA capable of being passed from one cell to another. The sharing of plasmid genes between individual bacteria and between bacterial lineages has contributed vastly to bacterial evolution, allowing specialized traits to 'jump ship' between one lineage or species and the next. The benefits of this generosity from the point of view of both recipient cell and plasmid are generally understood: plasmids receive new hosts and ride out selective sweeps across the population, recipient cells gain new traits (such as antibiotic resistance). Explaining this behavior from the point of view of donor cells is substantially more difficult. Donor cells pay a fitness cost in order to share plasmids, and run the risk of sharing advantageous genes with their competition and rendering their own lineage redundant, while seemingly receiving no benefit in return. Using both compartment based models and agent based simulations we demonstrate that 'secretive' genes which restrict horizontal gene transfer are favored over a wide range of models and parameter values, even when sharing carries no direct cost. 'Generous' chromosomal genes which are more permissive of plasmid transfer are found to have neutral fitness at best, and are generally disfavored by selection. Our findings lead to a peculiar paradox: given the obvious benefits of keeping secrets, why do bacteria share information so freely? | 2022 | 35603365 |
| 9703 | 15 | 0.9995 | Ecology and evolution of antibiotic resistance. The evolution of bacterial pathogens towards antibiotic resistance is not just a relevant problem for human health, but a fascinating example of evolution that can be studied in real time as well. Although most antibiotics are natural compounds produced by environmental microbiota, exposure of bacterial populations to high concentrations of these compounds as the consequence of their introduction for human therapy (and later on for farming) a few decades ago is a very recent situation in evolutionary terms. Resistance genes are originated in environmental bacteria, where they have evolved for millions of years to play different functions that include detoxification, signal trafficking or metabolic functions among others. However, as the consequence of the strong selective pressure exerted by antimicrobials at clinical settings, farms and antibiotic-contaminated natural ecosystems, the selective forces driving the evolution of these potential resistance determinants have changed in the last few decades. Natural ecosystems contain a large number of potential resistance genes; nevertheless, just a few of them are currently present in gene-transfer units and disseminated among pathogens. Along the review, the processes implied in this situation and the consequences for the future evolution of resistance and the environmental microbiota are discussed. | 2009 | 23765924 |
| 9533 | 16 | 0.9995 | The disparate effects of bacteriophages on antibiotic-resistant bacteria. Faced with the crisis of multidrug-resistant bacteria, bacteriophages, viruses that infect and replicate within bacteria, have been reported to have both beneficial and detrimental effects with respect to disease management. Bacteriophages (phages) have important ecological and evolutionary impacts on their bacterial hosts and have been associated with therapeutic use to kill bacterial pathogens, but can lead to the transmission of antibiotic resistance. Although the process known as transduction has been reported for many bacterial species by classic and modern genetic approaches, its contribution to the spread of antibiotic resistance in nature remains unclear. In addition, detailed molecular studies have identified phages residing in bacterial genomes, revealing unexpected interactions between phages and their bacterial hosts. Importantly, antibiotics can induce the production of phages and phage-encoded products, disseminating these viruses and virulence-related genes, which have dangerous consequences for disease severity. These unwanted side-effects of antibiotics cast doubt on the suitability of some antimicrobial treatments and may require new strategies to prevent and limit the selection for virulence. Foremost among these treatments is phage therapy, which could be used to treat many bacterial infectious diseases and confront the pressing problem of antibiotic resistance in pathogenic bacteria. This review discusses the interactions between bacteriophages, antibiotics, and bacteria and provides an integrated perspective that aims to inspire the development of successful antibacterial therapies. | 2018 | 30302018 |
| 9534 | 17 | 0.9994 | Defining the Benefits of Antibiotic Resistance in Commensals and the Scope for Resistance Optimization. Antibiotic resistance is a major medical and public health challenge, characterized by global increases in the prevalence of resistant strains. The conventional view is that all antibiotic resistance is problematic, even when not in pathogens. Resistance in commensal bacteria poses risks, as resistant organisms can provide a reservoir of resistance genes that can be horizontally transferred to pathogens or may themselves cause opportunistic infections in the future. While these risks are real, we propose that commensal resistance can also generate benefits during antibiotic treatment of human infection, by promoting continued ecological suppression of pathogens. To define and illustrate this alternative conceptual perspective, we use a two-species mathematical model to identify the necessary and sufficient ecological conditions for beneficial resistance. We show that the benefits are limited to species (or strain) interactions where commensals suppress pathogen growth and are maximized when commensals compete with, rather than prey on or otherwise exploit pathogens. By identifying benefits of commensal resistance, we propose that rather than strictly minimizing all resistance, resistance management may be better viewed as an optimization problem. We discuss implications in two applied contexts: bystander (nontarget) selection within commensal microbiomes and pathogen treatment given polymicrobial infections. IMPORTANCE Antibiotic resistance is commonly viewed as universally costly, regardless of which bacterial cells express resistance. Here, we derive an opposing logic, where resistance in commensal bacteria can lead to reductions in pathogen density and improved outcomes on both the patient and public health scales. We use a mathematical model of commensal-pathogen interactions to define the necessary and sufficient conditions for beneficial resistance, highlighting the importance of reciprocal ecological inhibition to maximize the benefits of resistance. More broadly, we argue that determining the benefits as well as the costs of resistances in human microbiomes can transform resistance management from a minimization to an optimization problem. We discuss applied contexts and close with a review of key resistance optimization dimensions, including the magnitude, spectrum, and mechanism of resistance. | 2023 | 36475750 |
| 4239 | 18 | 0.9994 | Bacterial resistance. Pathogenic bacteria remain adaptable to an increasingly hostile environment and a wider variety of more potent antibiotics. Organisms not intrinsically prepared for defense have been able to acquire resistance to newer antimicrobial agents. Chromosomal mutations alone cannot account for the rapid emergence and spread of antibiotic resistance. It has been established that plasmids and transposons are particularly important in the evolution of antibiotic-resistant bacteria. Plasmid- or transposon-mediated resistance provides the bacteria with pre-evolved genes refined to express high-level resistance. In particular, transposons can transfer these resistance determinants in diverse bacterial species, and nature provides in humans and animals large intestinal reservoirs in which such communications are facilitated. Antibiotic therapy exerts selection pressures on bacteria. Eradication or marked reduction in the populations of susceptible organisms promotes the overgrowth of intrinsically resistant strains and favors those resistant as a result of favorable chromosomal mutations or via plasmids or transposons. In our hospitals, where antibiotic consumption continues to increase, the nosocomial flora consists of many resistant bacteria, and infections acquired in the nosocomial setting are now far more severe than their community-acquired counterparts. There is convincing evidence that infection control measures must take into further consideration the contribution of the hospital worker as carrier and mediator of antibiotic resistance. | 1991 | 1649425 |
| 9130 | 19 | 0.9994 | Glycopeptide antibiotic resistance. Glycopeptide antibiotics are integral components of the current antibiotic arsenal that is under strong pressures as a result of the emergence of a variety of resistance mechanisms over the past 15 years. Resistance has manifested itself largely through the expression of genes that encode proteins that reprogram cell wall biosynthesis and thus evade the action of the antibiotic in the enterococci, though recently new mechanisms have appeared that afford resistance and tolerance in the more virulent staphylococci and streptococci. Overcoming glycopeptide resistance will require innovative approaches to generate new antibiotics or otherwise to inhibit the action of resistance elements in various bacteria. The chemical complexity of the glycopeptides, the challenges of discovering and successfully exploiting new targets, and the growing number of distinct resistance types all increase the difficulty of the current problem we face as a result of the emergence of glycopeptide resistance. | 2002 | 11807177 |